Role of duplicate genes in robustness against deleterious human mutations.
| Autor: | Tzu-Lin Hsiao, Dennis Vitkup |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: | |
| Zdroj: | PLoS Genetics, Vol 4, Iss 3, p e1000014 (2008) |
| Druh dokumentu: | article |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.1371/journal.pgen.1000014 |
| Popis: | It is now widely recognized that robustness is an inherent property of biological systems [1],[2],[3]. The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4],[5]. In this paper we investigate in detail the contribution of gene duplicates to back-up against deleterious human mutations. Our analysis demonstrates that the functional compensation by close homologs may play an important role in human genetic disease. Genes with a 90% sequence identity homolog are about 3 times less likely to harbor known disease mutations compared to genes with remote homologs. Moreover, close duplicates affect the phenotypic consequences of deleterious mutations by making a decrease in life expectancy significantly less likely. We also demonstrate that similarity of expression profiles across tissues significantly increases the likelihood of functional compensation by homologs. |
| Databáze: | Directory of Open Access Journals |
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